- In the Phase 2b trial, 100% (5 of
5) of ibezapolstat-treated patients who agreed to observation for
up to three months following Clinical Cure of CDI experienced no
recurrence of infection
- Further analyses will be forthcoming as data become available
regarding effects on bile acid metabolism and pharmacokinetic
data
- Preparation is underway for meetings with FDA, European
Medicines Agency and other global regulatory agencies and
advancement to international Phase 3 clinical trials
- Ibezapolstat has previously received FDA QIDP and Fast-Track
Designation
STATEN
ISLAND, N.Y., Jan. 29,
2024 /PRNewswire/ -- Acurx Pharmaceuticals, Inc.
(NASDAQ: ACXP) ("Acurx" or the "Company"), a late-stage
biopharmaceutical company developing a new class of small molecule
antibiotics for difficult-to-treat bacterial infections, today
announced positive extended clinical cure (ECC) data for
ibezapolstat (IBZ), its lead antibiotic candidate, from the
Company's recently completed Phase 2b
clinical trial in patients with CDI. This exploratory endpoint
showed that 12 patients who agreed to be followed up to three
months following Clinical Cure of their infection, 5 of 5 IBZ
patients experienced no recurrence of infection. In the vancomycin
control arm of the trial, 7 of 7 patients experienced no recurrence
of infection. ECC success is defined as a clinical cure at the TOC
visit (i.e., at least 48 hours post EOT) and no recurrence of CDI
within the 56 ± 2 days post EOT (ECC56) and 84 ± 2 days post EOT
(ECC84) in patients who consented to extended observation.
According to Dr. Garey: "CDI has long-term consequences
including poor quality of life for the patient. It's exciting to
see that the ibezapolstat Phase 2b
study followed patients for an extended time period to assure that
the ibezapolstat cure and anti-recurrence effects are long-lasting
and durable. This adds to the exciting microbiome data showing
replenishment of healthy microbiota that we have seen in our prior
studies."
Robert J. DeLuccia, Executive
Chairman of Acurx, stated: "This Extended Clinical Cure data
showing that no ibezapolstat-treated patient who achieved Clinical
Cure and consented to three months of post-treatment observation
experienced a recurrence of CDI during this period further
strengthens the ibezapolstat lineage of clinical success building
on our previously reported Phase 2 results of 96% Clinical Cure and
100% Sustained Clinical Cure along with favorable preservation of
the microbiome and no safety signals." He further stated: "We look
forward to advancing to Phase 3 clinical trials and are optimistic
about achieving non-inferiority versus vancomycin which is the
regulatory clinical development hurdle for marketing
registration".
David P. Luci, President &
CEO of Acurx, stated: "Ibezapolstat continues to demonstrate
success compared to a standard of care, oral vancomycin, to treat
patients with CDI. We anticipate continued favorable
differentiation between the two therapeutic
options in 2024. We expect to leverage this success in a
$1 billion plus US CDI global market
as we
move forward with an international Phase 3 clinical
trial mandate." He added: "The Company also
anticipates its price point for ibezapolstat, if approved, could
meet or beat other antibiotics recommended for use in treating
patients with CDI, thereby providing the whole package of clinical
comparability with microbiome health, safety and cost for patients
with this life-threatening disease."
About the Ibezapolstat Phase
2 Clinical Trial
The completed multicenter,
open-label single-arm segment (Phase 2a) study was
followed by a double-blind, randomized, active-controlled, non-inferiority, segment
(Phase 2b) at 28 US clinical
trial sites which together comprise the Phase 2 clinical
trial.(see https://clinicaltrials.gov/ct2/show/NCT04247542).
This Phase 2 clinical trial was designed to evaluate the clinical
efficacy of ibezapolstat in the treatment of CDI including
pharmacokinetics and microbiome changes from baseline and continue
to test for anti- recurrence microbiome properties seen in the
Phase 2a trial, including the treatment- related changes in alpha
diversity and bacterial abundance and effects on bile acid
metabolism.
The completed Phase 2a segment of this trial was an open label
cohort of up to 20 subjects from study centers
in the United States. In this cohort,
10 patients with diarrhea caused by C.
difficile were treated with ibezapolstat 450 mg orally, twice
daily for 10 days. All patients were followed for recurrence
for 28± 2 days. Per protocol, after 10 patients of the projected 20
Phase 2a patients completed treatment (100% cured infection at End
of Treatment), the Trial Oversight Committee assessed the safety
and tolerability and made its recommendation regarding early
termination of the Phase 2a study and advancement to the Ph2b
segment. The Company's Scientific Advisory Board concurred with
this recommendation.
In the now completed Phase 2b
trial segment, 32 patients with CDI were enrolled and randomized in
a 1:1 ratio to either ibezapolstat 450 mg every 12 hours or
vancomycin 125 mg orally every 6 hours,
in each case,
for 10 days and followed
for 28 ± 2 days following the end of
treatment for recurrence of CDI. The two treatments were identical
in appearance, dosing times, and number of capsules administered to
maintain the blind. The Company previously reported that the
overall
observed Clinical Cure rate in the combined
Phase 2 trials
in patients with CDI was 96% (25 out
of 26 patients), based on 10 out of 10 patients (100%) in Phase 2a
in the Modified Intent to Treat Population, plus 15 out of 16 (94%)
patients in Phase 2b in the Per
Protocol Population, who experienced Clinical Cure during treatment
with ibezapolstat. Ibezapolstat was well-tolerated, with three
patients each experiencing one mild adverse event assessed
by the blinded
investigator to be drug-related. All three events were gastrointestinal in nature
and resolved without treatment. There were no drug-related
treatment withdrawals or no drug-related serious adverse events, or
other safety findings of concern. In the Phase 2b vancomycin control arm, 14 out of 14 patients
experienced Clinical Cure. The Company is confident that based on
the pooled Phase 2 ibezapolstat Clinical Cure rate of 96% and the
historical vancomycin cure rate of approximately 81% (Vancocin®
Prescribing Information, January
2021), we will demonstrate non-inferiority of ibezapolstat
to vancomycin in Phase 3 trials in accordance with the applicable
FDA Guidance for Industry (October
2022).
The Phase 2b clinical trial
segment was discontinued due to success. The Company made this
decision in consultation with its medical and scientific advisors
and statisticians based on observed
aggregate blinded data and other
factors, including the cost to maintain clinical
trial sites and slow enrollment due to COVID-19 and its aftermath.
The Company had determined that the trial performed as anticipated
for both treatments, ibezapolstat and the control antibiotic
vancomycin (a standard of care to treat patients with CDI), with
high rates of clinical cure observed across the trial without any
emerging safety concerns. Accordingly, an Independent Data
Monitoring Committee was not required to perform an interim
analysis of this Phase 2b trial data
as originally planned. The Company anticipated that this decision
would allow the Company to advance this first-in-class,
FDA QIDP/Fast Track-designated antibiotic product candidate to
Phase 3 clinical trials more expeditiously.
The Phase 2b trial was originally
designed to be a non-inferiority (NI) trial and later amended to
include an interim efficacy analysis with review by an Independent
Data Monitoring Committee (IDMC). The decision to end the trial
early based on blinded clinical observations obviated the need for
an interim analysis, IDMC review, and NI assessment. The Company
determined, in consultation with its clinical and statistical
experts, that presenting clinical cure rates for the primary
efficacy endpoint is the most appropriate representation for the
clinical activity of ibezapolstat in treating CDI.
In the Phase 2 clinical trial, the Company will also evaluate
pharmacokinetics (PK) and microbiome changes and test for
anti-recurrence microbiome properties, including the change from
baseline in alpha diversity and bacterial abundance, especially
overgrowth of healthy gut microbiota Actinobacteria and Firmicute
phylum species during and after therapy. Phase 2a data demonstrated
complete eradication of colonic C. difficile by day
three of treatment with ibezapolstat as well as the observed
overgrowth of healthy gut microbiota, Actinobacteria and Firmicute
phyla species, during and after therapy. Very
importantly, emerging data show an increased concentration of secondary bile acids during
and following ibezapolstat therapy which is known to correlate with
colonization resistance
against C. difficile. A decrease in primary bile acids and the favorable
increase in the ratio of secondary-to-primary
bile acids suggest that ibezapolstat may reduce the likelihood of
CDI recurrence when compared to vancomycin.
About Ibezapolstat
Ibezapolstat is a novel,
orally administered antibiotic being developed as a Gram-Positive
Selective Spectrum (GPSS™) antibacterial. It is the first of a new
class of DNA polymerase IIIC inhibitors under development by
Acurx to treat bacterial infections. Ibezapolstat's unique spectrum
of activity, which includes C. difficile but spares other
Firmicutes and the important Actinobacteria phyla, appears to
contribute to the maintenance of a healthy gut microbiome.
In June 2018, ibezapolstat was
designated by the U.S. Food and Drug Administration (FDA) as a
Qualified Infectious Disease Product (QIDP) for the treatment of
patients with CDI and will be eligible to benefit from the
incentives for the development of new antibiotics established under
the Generating New Antibiotic Incentives Now (GAIN) Act. In January
2019, FDA granted
"Fast Track" designation to ibezapolstat for the treatment
of patients with CDI. The CDC has designated C.
difficile as an urgent threat highlighting the need for
new antibiotics to treat CDI.
About Clostridioides difficile Infection (CDI).
According to the 2017 Update (published February 2018) of the Clinical Practice
Guidelines for C. difficile Infection by the Infectious Diseases
Society of America (IDSA) and Society or Healthcare Epidemiology of
America
(SHEA), CDI remains a significant medical
problem in hospitals, in long-term care facilities
and in the community. C. difficile is one of the most
common causes of health care- associated infections in U.S.
hospitals (Lessa, et al, 2015, New England Journal of
Medicine). Recent estimates suggest
C. difficile approaches 500,000
infections annually in the U.S. and is associated with
approximately 20,000 deaths annually. (Guh, 2020, New England
Journal of Medicine). Based on internal estimates, the recurrence
rate for the antibiotics currently used to treat CDI is between 20%
and 40% among approximately 150,000 patients treated. We believe
the annual incidence of CDI in the U.S. approaches 600,000
infections and a mortality rate of approximately 9.3%.
About the Microbiome in C. difficile Infection (CDI)
and Bile Acid Metabolism
C. difficile can be a
normal component of the healthy gut microbiome, but when the
microbiome is thrown out of balance, the C.
difficile can thrive and cause an infection. After
colonization with C. difficile, the organism
produces and releases the main virulence factors, the two large
clostridial toxins A (TcdA) and B (TcdB). (Kachrimanidou,
Microorganisms 2020, 8,
200; doi:10.3390/microorganisms8020200.) TcdA and TcdB are
exotoxins that bind to human intestinal epithelial cells and are
responsible for inflammation, fluid and mucous secretion, as well
as damage to the intestinal mucosa.
Bile acids perform many functional roles
in the GI tract, with one of the most important being
maintenance of a healthy microbiome by inhibiting C.
difficile growth. Primary bile acids, which are secreted
by the liver into the intestines, promote germination of C.
difficile spores and thereby increase the risk of
recurrent CDI after successful treatment of an initial episode. On
the other hand, secondary bile acids, which are produced by normal
gut microbiota through metabolism of primary bile acids, do not
induce C. difficile sporulation and therefore protect
against recurrent disease. Since ibezapolstat treatment leads to
minimal disruption of the gut microbiome, bacterial production of
secondary bile acids continues which may contribute to an
anti-recurrence effect. Beneficial effects of bile acids
include a decrease
in primary bile acids and an increase
in secondary bile acids in patients with
CDI, which was observed in the Company's Ph2a trial results and
previously reported (CID, 2022).
About Acurx
Pharmaceuticals, Inc.
Acurx Pharmaceuticals is a late-stage biopharmaceutical company focused on developing a
new class of small molecule antibiotics for difficult-to-treat
bacterial infections. The Company's approach is to develop
antibiotic candidates with a Gram-positive selective spectrum
(GPSS®) that blocks the active site of the Gram+ specific bacterial
enzyme DNA polymerase IIIC (pol IIIC), inhibiting DNA replication
and leading to Gram-positive bacterial cell death. Its R&D
pipeline includes antibiotic product candidates that target
Gram-positive bacteria, including Clostridioides difficile,
methicillin-resistant Staphylococcus aureus (MRSA), vancomycin
resistant Enterococcus (VRE) and drug-resistant Streptococcus
pneumoniae (DRSP).
To learn more about
Acurx Pharmaceuticals and its product
pipeline, please visit www.acurxpharma.com
Forward-Looking Statements
Any statements in this
press release about our future expectations, plans and prospects,
including statements regarding our strategy, future operations,
prospects, plans and objectives, and other statements containing
the words "believes," "anticipates," "plans,"
"expects," and similar expressions, constitute forward-looking statements within the meaning
of The Private Securities Litigation Reform Act of 1995. Actual
results may differ materially from those indicated by such
forward-looking statements as a result of various important
factors, including: whether ibezapolstat will benefit from the QIDP
designation; whether ibezapolstat will advance through the clinical
trial process on a timely basis; whether the results of the
clinical trials of ibezapolstat will warrant the submission of
applications for marketing approval, and if so, whether
ibezapolstat will receive approval from the FDA or equivalent
foreign regulatory agencies where approval is sought; whether, if
ibezapolstat obtains approval, it will be successfully distributed
and marketed; and other risks and uncertainties described in the
Company's annual report filed with the Securities and Exchange
Commission on Form 10-K for the year ended December 31, 2022, and in the Company's
subsequent filings with the Securities and Exchange Commission.
Such forward- looking statements speak only as of the date of this
press release, and Acurx disclaims any intent or obligation to
update these forward-looking statements to reflect events or
circumstances after the date of such statements, except as may be
required by law.
Investor Contact: Acurx
Pharmaceuticals, Inc.
David P.
Luci, President & CEO
Tel: 917-533 1469
Email: davidluci@acurxpharma.com
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SOURCE Acurx Pharmaceuticals, Inc.